Current state of the art dialysis therapy for end stage renal disease patients is associated with frequent severe hypotension, muscle cramping and fatigue. This morbidity limits patient rehabilitation and increases cost due to the need for higher staff/patient ratios. Intradialytic morbidity is known to be dependent on Na and H20 removal rates and associated rates of circulating plasma volume depletion. Morbidity also seems to be dependent on the magnitude of acetate accumulation in the patient which appears to reduce cardiac output and total peripheral resistance. Currently dialysis is prescribed to achieve zero H20 balance over each treatment cycle (end of 1 dialylsis to the end of next sequential dialysis) but Na balance and acetate accumulation are not considered in the prescription. Consequently end dialysis Na depletion or excess may result as well as substantial variability in the magnitude of acetate accumulation. Kinetic models of Na, H20 and buffer fluxes during dialysis have been developed to prescribe therapy which results in zero Na and H20 balance over each treatment cycle and known magnitudes of acetate accumulation. Additionally, the models have been designed to remove Na and H20 simultaneously (as is conventionally done) or to remove Na and H20 sequentially during dialysis with complete time separation of net Na and H20 flux. The rate of plasma volume depletion (and hence magnitude of morbidity) is calculated to be much slower with time separation of Na and H20 removal compared to simultaneous isotonic removal. The proposed research is designed to compare the physiologic response (Delta plasma volulme) and intradialytic morbidity with state of the art dialysis to kinetically modeled therapy. Interdialytic morbidity (hypertension and fluid overload) will also be compared at 2 levels of end dialysis body Na content corresponding to modeled end dialysis serum Na's of 140 an 145 mEq/L. Finally, the effects of substituting bicarbonate for acetate dialysate buffer on morbidity with kinetically modeled therapy will be studied.